Influenza virus infection normally does not result in a serious disease. However, in an immunoincompetent (elderly, immunodeficient, immunosuppressed) host it may predispose the individual to a secondary bacterial infection or cause pathology or morbidity in its own right. Prior to or in the absence of presence of an adequate immune response on the lung, alternative mechanisms of pulmonary defense may be important in limiting viral (influenza) infection. A major defense mechanism in controlling pulmonary virus infections could be the Natural Killer cell. The purpose of our research plan is to study the development and role of Natural Killer (NK) cells to influenza virus infections in the lung. Studies will include both functional and morphologic approaches. It is known that influenza virus will induce Interferons that are capable of augmenting NK cell activity. It is not known if this induction and/or augmentation is a local and/or systemic phenomenon. This research grant proposes to study the regional magnitude of both the induction of interferon and the augmentation of NK activity during influenza infection. It is known that NK cells reside in the lung. Pulmonary NK cells are capable of clearing/or lysing radiolabeled target cells in vivo and in vitro, respectively. It is not known where the NK cells reside in the lung. We will continue our investigations to characterize NK cells in the lung using the electron microscope and other morphologic techniques including immunoperoxidase. We will attempt to identify where NK cells reside in the lung, i.e., blood vessels, interstitium alveolar spaces. Knowing the answer to this question is important toward understanding how the lung is protected against virus infections and tumor metastases. In addition the contribution of NK cells to the pathology or protection from influenza virus infection will be studied by in vitro techniques using physical separations, functional depletion studies, and reconstitution experiments for identifying subpopulations of cells that may be involved in lysis of virus infected targets. Results from studies of natural killer cells present, augmented or "recruited" to the lung prior to, or in response to pulmonary influenza infection in experimental animal models (mice/hamster), could contribute to understanding pulmonary defense mechanisms to virus infections in general.